Magnetic Resonance Imaging and Spectroscopy (MRI, MRS) can be used to obtain detailed physiologic and metabolic information regarding tumors. Diffuse Optical Spectroscopy and Tomography (DOS, DOT = SDOT) can provide unique and complementary information regarding tumor physiology and metabolism. Simultaneous employment of both MR and optical modalities may offer new insight that is unavailable by use of either of these techniques alone. During the past two years, based on funding under an NCI Pre-ICMIC grant, we have built a broadband frequency domain photon migration probe (FDPM) that is compatible with high magnetic fields, operates inside a 4 Tesla MR system, and provides simultaneous optical/MR measurements in small animals. Before such a system can be widely used in clinical cancer studies, we believe it is essential to validate our measurements and develop a detailed understanding of the factors that influence MRI-optics co-registration. One of the limitations for undertaking such a study is the fact that nontomographic optical measurement techniques have poor spatial localization that is due to their broad point spread function and ambiguity in the origin of the detected signals. Consequently, there is a great need to understand the underlying relationship between optical and MR signals. Once this relationship is clarified, the spatial localization of optical measurements can be improved and functional information can be accurately assigned to discrete tumor tissue structures. The long-term goal of this project is to construct an MR-compatible optical spectroscopic tomography system for improved spatial localization of optical measurements and accurate opticaI-MRI co-registration. Such a system can be scaled up for human studies of cancer. During the R21 phase (Year 01) we will expand the current single transmitter/receiver optical system to an MR compatible multi-wavelength, multi-detector system and optimize its performance for SDOT. During this process, different geometries, detectors, data acquisition techniques, and image inversion strategies will be explored. In the subsequent R33 phase (Years 02-04) of the application, we will pursue the following aims: 1) design and construct a full scale small animal MR-SDOT system, 2) using the constructed system investigate the relationship between MRI/MRS and optical measurements to improve the spatial localization in SDOT, 3) employ the developed dual imaging system for combined dynamic contrast enhanced functional imaging of tumors in animal models.